ArticleJournal of neuroinflammation2011
Increased expression of cystine/glutamate antiporter in multiple sclerosis.
Article in Journal of neuroinflammation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 111 citations in OpenAlex.
- Ginkgo biloba does not improve cognitive function in MS: a randomized placebo-controlled trial.Neurology · 2012Trial
- Cerebrospinal fluid amino acid alterations are associated with oxidative stress and neuronal injury markers in multiple sclerosis.Metabolic brain disease · 2026Article
- Intact corticostriatal function in aged system xTranslational psychiatry · 2025Article
- The Crosstalk Between Ferritinophagy and Ferroptosis in Ischemic Stroke: Regulatory Mechanisms and Therapeutic Implications.Cellular and molecular neurobiology · 2025Review
- Disulfidptosis: a new target for central nervous system disease therapy.Frontiers in neuroscience · 2025Review
- Role of bisphenol A in the aberrant activation of ionotropic glutamate transporters in the cerebral cortex and altered behavioral responses in C57BL/6J mice.Frontiers in toxicology · 2025Article
- Implication of system xJournal of neuroinflammation · 2024Article
- Single-Cell Multi-Omics Map of Cell Type-Specific Mechanistic Drivers of Multiple Sclerosis Lesions.Neurology(R) neuroimmunology & neuroinflammation · 2024Article
- Targeted RNAseq Revealed the Gene Expression Signature of Ferroptosis-Related Processes Associated with Disease Severity in Patients with Multiple Sclerosis.International journal of molecular sciences · 2024Article
- Progress of Ferroptosis in Ischemic Stroke and Therapeutic Targets.Cellular and molecular neurobiology · 2024Review
- RIPK1 activation in Mecp2-deficient microglia promotes inflammation and glutamate release in RTT.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
- Astrocytic scar restricting glioblastoma via glutamate-MAO-B activity in glioblastoma-microglia assembloid.Biomaterials research · 2023Article
- Influence of Auditory Integrative Training on Casein Kinase 2 and Its Impact on Behavioral and Social Interaction in Children with Autism Spectrum Disorder.Current issues in molecular biology · 2023Article
- Unveiling tumor immune evasion mechanisms: abnormal expression of transporters on immune cells in the tumor microenvironment.Frontiers in immunology · 2023Review
- A Narrative Review on Axonal Neuroprotection in Multiple Sclerosis.Neurology and therapy · 2022Review
- Ferroptosis promotes T-cell activation-induced neurodegeneration in multiple sclerosis.Cellular & molecular immunology · 2022Article
- The Role of SLC7A11 in Cancer: Friend or Foe?Cancers · 2022Review
- Retinal Glutamate Neurotransmission: From Physiology to Pathophysiological Mechanisms of Retinal Ganglion Cell Degeneration.Life (Basel, Switzerland) · 2022Review
- Targeting N-type calcium channels in young-onset of some neurological diseases.Frontiers in cell and developmental biology · 2022Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter x(c)⁻, an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system x(c)⁻ in glutamate homeostasis alterations in MS pathology.
methodsPrimary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT) was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE), the animal model of MS, and in samples of MS patients. RESULTS AND DISCUSSION: We show here that human activated monocytes release glutamate through cystine/glutamate antiporter x(c)⁻ and that the expression of the catalytic subunit xCT is upregulated as a consequence of monocyte activation. In addition, xCT expression is also increased in EAE and in the disease proper. In the later, high expression of xCT occurs both in the central nervous system (CNS) and in peripheral blood cells. In particular, cells from monocyte-macrophage-microglia lineage have higher xCT expression in MS and in EAE, indicating that immune activation upregulates xCT levels, which may result in higher glutamate release and contribution to excitotoxic damage to oligodendrocytes.
conclusionsTogether, these results reveal that increased expression of the cystine/glutamate antiporter system x(c)⁻ in MS provides a link between inflammation and excitotoxicity in demyelinating diseases.
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